Neuronal activity in cerebellar cortex related to control of prehensile force.
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Staggerer mice (sg/sg) have a severe ataxia correlated with cerebellar Purkinje cell anomalies and granule cell death. Previous studies of adult staggerer----wild-type chimeric mice have revealed that the mutant Purkinje cell defects visible in the light microscope (small size, ectopia and reduced number) are intrinsic properties of sg/sg Purkinje cells, while the granule cell death observed in the mutant is not an intrinsic property of sg/sg granule cells. In this report we continue the study of granule cell death and examine the phenotype, observed in staggerer mutants, of the developmental persistence of the external granular layer (EGL). Four staggerer----wild-type mouse chimeras were examined at 16 or 17 days of postnatal age. Most showed intermediate amounts of granule cell pycnosis and all showed intermediate expression of EGL persistence. There was little correlation observed between the amount of granule cell pycnosis and either the genotype of the immediately underlying Purkinje cells, or the proportion of staggerer cells in the chimera as a whole (determined by the genotype ratio of other brain regions and by coat melanocytes). While the presence or absence of an EGL did not correlate with the genotype of the immediately adjacent Purkinje cells, there was good agreement between the extent of persistence of the EGL and the overall contribution of staggerer cells to the chimera. The results suggest that the intermediate numbers of granule cells observed in adult staggerer chimeras are the result of both reduced granule cell genesis and increased pruning by cell death. The findings are further discussed in terms of two possible models of staggerer gene action.
The cerebellar molecular layer of chronic alcohol treated rats showed degenerated parallel fiber boutons and vacated Purkinje cell spines after 6 months of alcohol feeding; degenerated Purkinje cell dendrites were concomitantly observed. The number of synapses between parallel fibers and Purkinje cell spines decreased after 6 months whereas their mean synaptic diameter increased throughout the experiment. Conversely, synapses between parallel fibers and dendrites of interneurons increased in 18-month alcohol-fed group. Quantifications were done using a discrete unfolding procedure. It was also observed that some parallel fiber terminals simultaneously established synapses with multiple Purkinje cell spines and with dendrites of interneurons. These results were obtained from groups of 6 rats alcohol-fed for 1, 3, 6, 12 and 18 months and compared with age-matched pair-fed controls. Previous reports of alcohol-induced degenerative changes in the adult rat central nervous system were, thus, fully corroborated. Furthermore, there was evidence of remodeling processes pointing to compensatory plastic mechanisms in the cerebellar circuitry albeit not sufficient to overcome its alcohol-induced deterioration.
The maturation of the intermediate cell of Lugaro, impregnated by classical silver methods, was studied on parasagittal sections of cerebellar vermis of newborn rat pups. Using morphological criteria characteristic of the adult cell type, immature Lugaro neurons can be recognized from the second part of the first postnatal week on. This implies that these cells differentiate at a much earlier age than previously inferred from studies using tritiated thymidine.
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